The overall objective of this experimental program is increased understanding of cellular functions and intercellular relationships within the lymphoreticular system, both as developmental phenomena and as they moderate host responses to internal and external sources of antigenic challenge. More specifically, efforts will be made a) to understand better the mechanisms of primary in vitro responses in mouse, rat, and human systems to mitogens, alloantigens, and other membrane antigens, b) to attempt to correlate these effects with in vivo phenomena, and c) to explain the striking developmental changes in reactivity patterns which have been found. Changes in the organ distribution of various marked components of the lymphoreticular system, such as the T cell and its subpopulations, will be examined during continuing as well as discontinuous antigenic challenges. A major focus will be upon systems of apparent tolerance in which continuous sources of antigen are a major factor in the host- antigen relationship, such as tissue chimeric states and tumor-bearing. Such systems are of intrinsic interest but are also important because they reflect upon antigenic competition in respect to capacity to respond to other antigenic challenges, possibly as models for the state of immunologic homeostasis with respect to internal or self antigens. These studies should contribute to better understanding of host- parasite relationships, developmental events involving chimerism, the tumor-host relationship, and other forms of immunologic homeostasis.